Antibody–drug conjugates in selected solid tumours: a position statement update based on findings from the third workshop held by the ETOP IBCSG Partners Foundation
ESMO Open, vol. 11, pp. 108316
Abstract
The European Thoracic Oncology Platform (ETOP) International Breast Cancer Study Group (IBCSG) Partners Foundation initiated a series of workshops for experts to review current evidence and offer recommendations to guide future antibody-drug conjugate (ADC) research. Here, we summarise key findings from the third workshop, which included experts in various solid tumours, basic/translational research scientists and pharmaceutical industry representatives. Recent positive phase III trial data have further incorporated ADCs into the standard of care [e.g. lung: sacituzumab tirumotecan; breast: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan, datopotamab deruxtecan; muscle-invasive bladder cancer: enfortumab vedotin; ovarian cancer: mirvetuximab soravastine; cervical cancer: tisotumab vedotin]. Thus, research priorities must be tailored according to tumour type, potentially focussing initially on settings where ADCs could replace chemotherapy. Many phase III ADC trials have been initiated based on positive phase I data and although these trials are larger than those conducted historically, prespecified criteria (e.g. patient numbers and magnitude of efficacy) should be met to justify proceeding directly to phase III. Importantly, although several ADCs have been successfully developed without mandatory biomarker selection, biomarker-driven ADC development enables rational patient selection, as illustrated by multiple ADCs (e.g. T-DXd, mirvetuximab soravtansine and telisotuzumab vedotin). The identification, development and validation of predictive biomarkers are therefore essential, particularly given several critical nuances, including the algorithms used to assess biomarker status and the type of specimen analysed, all of which may be influenced by temporal and spatial heterogeneity. Additional ADC research priorities include the optimisation of ADC constructs to enhance efficacy/tolerability and the identification of reliable ADC targets, including work to elucidate attributes of already-identified targets. Finally, considering the vast amount of ADC-related data being generated, artificial intelligence could be leveraged to analyse combined datasets and generate composite biomarkers, including tumour histology, optimal target expression thresholds, molecular alterations and activated pathways affecting payload activity and target function, to accelerate research.
Authors 29
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Centre Hospitalier Universitaire Vaudois
Affiliation as printed
Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address: https://twitter.com/peters_solange
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Centre Hospitalier Universitaire Vaudois
Affiliation as printed
Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
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Université Paris-Saclay · Institut Gustave Roussy
Affiliation as printed
Department of Medical Oncology, Gustave Roussy, Villejuif, France; Université Paris-Saclay, Villejuif, France
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Memorial Sloan Kettering Cancer Center
Affiliation as printed
Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
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Affiliation as printed
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. Electronic address: https://twitter.com/Alex_Azizi_
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Royal Marsden NHS Foundation Trust · Institute of Cancer Research
Affiliation as printed
Gynaecology Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK
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The Netherlands Cancer Institute
Affiliation as printed
Department of Thoracic Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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University of Milan · European Institute of Oncology
Affiliation as printed
Division of Early Drug Development, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. Electronic address: https://twitter.com/curijoey
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Memorial Sloan Kettering Cancer Center
Affiliation as printed
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. Electronic address: https://twitter.com/joshdragomd
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Sarah Cannon Research Institute
Affiliation as printed
Drug Development Unit, Sarah Cannon Research Institute, London, UK
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University of California, Los Angeles
Affiliation as printed
David Geffen School of Medicine, University of California, Los Angeles, USA
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University of Bonn · University Hospital Bonn
Affiliation as printed
Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Bonn; Department of Urology, University Hospital Bonn (UKB), Bonn, Germany; Institute of Experimental Oncology, University Hospital Bonn (UKB), Bonn, Germany. Electronic address: https://twitter.com/niklas_kluemper
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Institut national de recherche en sciences et technologies du numérique · Inserm · Université Paris-Saclay · Institut Gustave Roussy · CentraleSupélec
Affiliation as printed
IHU PRISM National PRecISion Medicine Center in Oncology, Gustave Roussy, Villejuif, France; Molecular Predictors and New Targets in Oncology, INSERM U981, Gustave Roussy, Villejuif, France; Centre for Visual Computing, CentraleSupélec, Inria, Université Paris-Saclay, Gif-Sur-Yvette, France
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Hospital Universitario 12 De Octubre
Affiliation as printed
Department of Pathology, Hospital Universitario 12 de Octubre, Madrid, Spain
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Affiliation as printed
4th Department of Medical Oncology and Clinical Trials Unit, Henry Dunant Hospital Center, Athens, Greece. Electronic address: https://twitter.com/g_mountzios
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European Institute of Oncology
Affiliation as printed
Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: https://twitter.com/APassaroMD
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Hospital Universitario 12 De Octubre
Affiliation as printed
Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: https://twitter.com/lpazares
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Affiliation as printed
Department of Medical Oncology, Gustave Roussy, Villejuif, France; IHU PRISM National PRecISion Medicine Center in Oncology, Gustave Roussy, Villejuif, France. Electronic address: https://twitter.com/BarbaraPistill2
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Queen Mary University of London · National Institute for Health and Care Research · Barts Cancer Institute
Affiliation as printed
Barts Cancer Institute, National Institute for Health Research Biomedical Research Centre, Queen Mary University of London, London, UK. Electronic address: https://twitter.com/etop_ibcsg
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Affiliation as printed
Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain. Electronic address: https://twitter.com/nreguart
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Institut Gustave Roussy · Fondation Gustave Roussy
Affiliation as printed
Department of Cancer Medicine, Gustave Roussy, Villejuif, France
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Novartis (Switzerland) · Novartis Institutes for BioMedical Research
Affiliation as printed
Novartis Biomedical Research, Basel, Switzerland
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Bicycle Therapeutics (United Kingdom)
Affiliation as printed
Bicycle Therapeutics Ltd, Cambridge, UK
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Leiden University Medical Center
Affiliation as printed
Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, The Netherlands
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NIHR Oxford Biomedical Research Centre
Affiliation as printed
NIHR Biomedical Research Centre, Oxford, UK. Electronic address: https://twitter.com/lizzysmyth1
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Cancer Research UK · University College London
Affiliation as printed
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK; Department of Oncology, University College London Hospitals, London, UK
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Universitair Ziekenhuis Leuven · KU Leuven
Affiliation as printed
Department of Digestive Oncology, University Hospital Gasthuisberg and University of Leuven (KUL), Leuven, Belgium
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The University of Melbourne · Peter MacCallum Cancer Centre
Affiliation as printed
Department of Cancer Research, Peter MacCallum Cancer Center, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Center, Melbourne, Australia; The Sir Peter MacCallum Department of Medical Oncology, The University of Melbourne, Parkville, Australia
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Rolf Arno Stahel corresponding
International Breast Cancer Study Group
Affiliation as printed
Coordinating Center, ETOP IBCSG Partners Foundation, Bern, Switzerland. Electronic address: rolf.stahel@etop.ibcsg.org
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